Euglycemic clamp studies

In single-dose, double-bhnd, euglycemic clamp studies, insulin glargine had a smoother metabolic effect with a peakless profile of action starting at 2-4 hours and continuing over 24 hours than protamine zinc insulin, whose peak occurred at 4 hours and whose activity subsequently fell (12). 

Fig. 12.2 Pharmacokinetic-pharmacodynamic modeling of pharmacokinetics (left panel) and glucodynamics (right panel) in a healthy volunteer receiving regular human insulin in a euglycemic clamp study (from [43]).

Apweiler et al. (1995) administered BM 13.09143 to lean and obese Zucker rats and performed hyperinsulinemic-euglycemic clamp studies in these animals. 

Dose-ranging Euglycemic Clamp Study in Subjects with Type 1 Diabetes... 

For the assessment of the side effect potential of the candidate compound on peripheral insulin sensitivity, multiple oGTTs can be performed during the treatment period or the animal study is finished by a hyperinsulinemic-euglycemic glucose clamp study. 

CRITICAL ASSESSEMENT OF THE METHOD The results of metabolic tissue parameters in liver, and muscle must be interpreted carefully, when a hyperinsulinemic-euglycemic glucose clamp study is performed at the end of the treatment period. Under clamp conditions these tissue parameters are mainly influenced by the hyperinsulinemic condition during the clamp study than by the compound s effect itself. 

All subjects were assessed over four test periods, 3 to 14 days apart, to determine dose-ranging effects and pharmacodynamics by euglycemic clamp, and insulin pharmacokinetics over 6 hours. Oralin administration on the three study days was in randomized order. Each subject was provided with the placebo device to practice the administration technique as taught by a video demonstration. The Ora-lin device comprises a standard MDI device with certain proprietary modifications to deliver the insulin into patienfs mouth. A simple procedure was used for Oralin dosing patients were asked to position the device in their mouth and to spray the Ora-lin formulation by depressing the device once. Patients were asked not to exhale or... 

The study [83] investigated whether resveratrol can improve nonalcoholic fatty liver disease (NAFLD) and evaluated the possible mechanism. Rats fed a high-fat diet were treated with resveratrol and the liver histology was observed. Hyperinsulinemic euglycemic clamp was performed to assess insulin sensitivity. Fat accumulation was induced in FIepG2 cells, and the cells were treated with RSV. AMP-activated protein kinase phosphorylation levels were detected both in the animal study and cell study. Rats fed a high-fat diet developed abdominal obesity, NAFLD, and insulin resistance, which were markedly improved by 10 week. 

Pospisilik JA, Stafford SG, Demufh H-U, McIntosh CHS, Pederson RA (2002) Long-term treatment with dipeptidyl peptidase IV inhibitor improves hepatic and peripheral insulin sensitivity in the VDF Zucker rat a euglycemic-hyperinsulinemic clamp study. Diabetes... 

A brief overview about the fundamental principles of the pathogenesis of skeletal muscle insulin resistance and its contribution to the development of type 2 diabetes mellitus is given in the following. Priority is given to the role of lipid metabolism, which is the main field of the reported spectroscopic studies. Furthermore, the technique of euglycemic hyperinsulinemic glucose clamp is described allowing determination of the individual insulin sensitivity of musculature. The role of IMCL in insulin resistance of the skeletal muscle is discussed. 

The effects of counterregulatory hormones on insulin-induced glucose utilization by individual tissues in rats, using the euglycemic hyperinsulinemic clamp technique combined with an injection of 2-[l-3H]-deoxyglucose, were studied by Marfaing et al. (1991). 

Lee et al. (1994) studied the metabolic effects of troglitazone on fructose-induced insulin resistance with the euglycemic hyperinsulinemic clamp technique in rats. 

Hulman et al. (1993) studied insulin resistance in the conscious spontaneously hypertensive rat with the euglycemic hyperinsulinemic clamp technique. 

Lee and Olefsky (1995) studied the effects of troglitazone in normal rats with the euglycemic glucose clamp technique. 

Zinker, B. A., Allison, R. G., Ijcy, D. B., and Wasserman, D. H. (1997). Interaction of exercise, insulin, and hypoglycemia studied using euglycemic and hypoglycemic insulin clamps. Am. PftystaJ. 272, E530-E542. 

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